Antiviral Innate Responses Induced by VSV-EBOV Vaccination Contribute to Rapid Protection

ABSTRACT Ebola virus (EBOV) is a single-stranded RNA virus that causes Ebola virus disease (EVD), characterized by excessive inflammation, lymphocyte apoptosis, hemorrhage, and coagulation defects leading to multiorgan failure and shock. Recombinant vesicular stomatitis virus expressing the EBOV gly...

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Autores principales:	Andrea R. Menicucci, Allen Jankeel, Heinz Feldmann, Andrea Marzi, Ilhem Messaoudi
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2019
Materias:	VSV-EBOV Ebola virus filovirus macaque vaccine Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/22b8b5e8b08d41a8839aae168a0e384a
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spelling	oai:doaj.org-article:22b8b5e8b08d41a8839aae168a0e384a2021-11-15T15:55:24ZAntiviral Innate Responses Induced by VSV-EBOV Vaccination Contribute to Rapid Protection10.1128/mBio.00597-192150-7511https://doaj.org/article/22b8b5e8b08d41a8839aae168a0e384a2019-06-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.00597-19https://doaj.org/toc/2150-7511ABSTRACT Ebola virus (EBOV) is a single-stranded RNA virus that causes Ebola virus disease (EVD), characterized by excessive inflammation, lymphocyte apoptosis, hemorrhage, and coagulation defects leading to multiorgan failure and shock. Recombinant vesicular stomatitis virus expressing the EBOV glycoprotein (VSV-EBOV), which is highly efficacious against lethal challenge in nonhuman primates, is the only vaccine that successfully completed a phase III clinical trial. Additional studies showed VSV-EBOV provides complete and partial protection to macaques immunized 7 and 3 days before EBOV challenge, respectively. However, the mechanisms by which this live-attenuated vaccine elicits rapid protection are only partially understood. To address this, we carried out a longitudinal transcriptome analysis of host responses in whole-blood samples collected from cynomolgus macaques vaccinated with VSV-EBOV 28, 21, 14, 7, and 3 days before EBOV challenge. Our findings indicate the transcriptional response to the vaccine peaks 7 days following vaccination and contains signatures of both innate antiviral immunity as well as B-cell activation. EBOV challenge 1 week after vaccination resulted in large gene expression changes suggestive of a recall adaptive immune response 14 days postchallenge. Lastly, the timing and magnitude of innate immunity and interferon-stimulated gene expression correlated with viral burden and disease outcome in animals vaccinated 3 days before challenge. IMPORTANCE Ebola virus (EBOV) is the causative agent of Ebola virus disease (EVD), a deadly disease and major public health threat worldwide. A safe and highly efficacious vesicular stomatitis virus-based vaccine against EBOV is the only platform that has successfully completed phase III clinical trials and has been used in recent and ongoing outbreaks. Earlier studies showed that antibodies are the main mode of protection when this vaccine is administered 28 days before EBOV challenge. Recently, we showed this vaccine can provide protection when administered as early as 3 days before challenge and before antibodies are detected. This study seeks to identify the mechanisms of rapid protection, which in turn will pave the way for improved vaccines and therapeutics. Additionally, this study provides insight into host gene expression signatures that could provide early biomarkers to identify infected individuals who are at highest risk of poor outcomes.Andrea R. MenicucciAllen JankeelHeinz FeldmannAndrea MarziIlhem MessaoudiAmerican Society for MicrobiologyarticleVSV-EBOVEbola virusfilovirusmacaquevaccineMicrobiologyQR1-502ENmBio, Vol 10, Iss 3 (2019)
institution	DOAJ
collection	DOAJ
language	EN
topic	VSV-EBOV Ebola virus filovirus macaque vaccine Microbiology QR1-502
spellingShingle	VSV-EBOV Ebola virus filovirus macaque vaccine Microbiology QR1-502 Andrea R. Menicucci Allen Jankeel Heinz Feldmann Andrea Marzi Ilhem Messaoudi Antiviral Innate Responses Induced by VSV-EBOV Vaccination Contribute to Rapid Protection
description	ABSTRACT Ebola virus (EBOV) is a single-stranded RNA virus that causes Ebola virus disease (EVD), characterized by excessive inflammation, lymphocyte apoptosis, hemorrhage, and coagulation defects leading to multiorgan failure and shock. Recombinant vesicular stomatitis virus expressing the EBOV glycoprotein (VSV-EBOV), which is highly efficacious against lethal challenge in nonhuman primates, is the only vaccine that successfully completed a phase III clinical trial. Additional studies showed VSV-EBOV provides complete and partial protection to macaques immunized 7 and 3 days before EBOV challenge, respectively. However, the mechanisms by which this live-attenuated vaccine elicits rapid protection are only partially understood. To address this, we carried out a longitudinal transcriptome analysis of host responses in whole-blood samples collected from cynomolgus macaques vaccinated with VSV-EBOV 28, 21, 14, 7, and 3 days before EBOV challenge. Our findings indicate the transcriptional response to the vaccine peaks 7 days following vaccination and contains signatures of both innate antiviral immunity as well as B-cell activation. EBOV challenge 1 week after vaccination resulted in large gene expression changes suggestive of a recall adaptive immune response 14 days postchallenge. Lastly, the timing and magnitude of innate immunity and interferon-stimulated gene expression correlated with viral burden and disease outcome in animals vaccinated 3 days before challenge. IMPORTANCE Ebola virus (EBOV) is the causative agent of Ebola virus disease (EVD), a deadly disease and major public health threat worldwide. A safe and highly efficacious vesicular stomatitis virus-based vaccine against EBOV is the only platform that has successfully completed phase III clinical trials and has been used in recent and ongoing outbreaks. Earlier studies showed that antibodies are the main mode of protection when this vaccine is administered 28 days before EBOV challenge. Recently, we showed this vaccine can provide protection when administered as early as 3 days before challenge and before antibodies are detected. This study seeks to identify the mechanisms of rapid protection, which in turn will pave the way for improved vaccines and therapeutics. Additionally, this study provides insight into host gene expression signatures that could provide early biomarkers to identify infected individuals who are at highest risk of poor outcomes.
format	article
author	Andrea R. Menicucci Allen Jankeel Heinz Feldmann Andrea Marzi Ilhem Messaoudi
author_facet	Andrea R. Menicucci Allen Jankeel Heinz Feldmann Andrea Marzi Ilhem Messaoudi
author_sort	Andrea R. Menicucci
title	Antiviral Innate Responses Induced by VSV-EBOV Vaccination Contribute to Rapid Protection
title_short	Antiviral Innate Responses Induced by VSV-EBOV Vaccination Contribute to Rapid Protection
title_full	Antiviral Innate Responses Induced by VSV-EBOV Vaccination Contribute to Rapid Protection
title_fullStr	Antiviral Innate Responses Induced by VSV-EBOV Vaccination Contribute to Rapid Protection
title_full_unstemmed	Antiviral Innate Responses Induced by VSV-EBOV Vaccination Contribute to Rapid Protection
title_sort	antiviral innate responses induced by vsv-ebov vaccination contribute to rapid protection
publisher	American Society for Microbiology
publishDate	2019
url	https://doaj.org/article/22b8b5e8b08d41a8839aae168a0e384a
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Antiviral Innate Responses Induced by VSV-EBOV Vaccination Contribute to Rapid Protection

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